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Functional connectivity changes of the hippocampal subregions in anti-N-methyl-D-aspartate receptor encephalitis

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Abstract

The hippocampus plays an important role in the pathophysiological mechanism of Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. Nevertheless, the connection between the resting-state activity of the hippocampal subregions and neuropsychiatric disorders in patients remains unclear. This study aimed to explore the changes in functional connectivity (FC) in the hippocampal subregions of patients with anti-NMDAR encephalitis and its association with clinical symptoms and cognitive performance. Twenty-three patients with anti-NMDAR encephalitis and 23 healthy controls (HC) were recruited. All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans and completed clinical cognitive scales. Based on the Brainnetome Atlas, the rostral (anterior) and caudal (posterior) hippocampi of both the left and right hemispheres were selected as regions of interest (ROIs) for FC analysis. First, a one-sample t-test was used to observe the whole-brain connectivity distribution of hippocampal subregions within the patient and HC groups at a threshold of p < 0.05. The two-sample t-test was used to compare the differences in hippocampal ROIs connectivity between groups, followed by a partial correlation analysis between the FC values of brain regions with statistical differences and clinical variables. This study observed that the distribution of whole-brain functional connectivity in the rostral and caudal hippocampi aligned with the connectivity differences between the anterior and posterior hippocampi. Compared to the HC group, the patients showed significantly decreased FC between the bilateral rostral hippocampus and the left inferior orbitofrontal gyrus and between the right rostral hippocampus and the right cerebellum. However, a significant increase in FC was observed between the right rostral hippocampus and left superior temporal gyrus, the left caudal hippocampus and right superior frontal gyrus, and the right caudal hippocampus and left gyrus rectus. Partial correlation analysis showed that FC between the left inferior orbitofrontal gyrus and the right rostral hippocampus was significantly negatively correlated with the California Verbal Learning Test (CVLT) and Brief Visuospatial Memory Test (BVMT) scores. The FC between the right rostral hippocampus and the left superior temporal gyrus was negatively correlated with BVMT scores. FC abnormalities in the hippocampal subregions of patients with anti-NMDAR encephalitis were associated with cognitive impairment, emotional changes, and seizures. These results may help explain the pathophysiological mechanisms and clinical manifestations of anti-NMDAR encephalitis and NMDAR dysfunction-related diseases such as schizophrenia.

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The de-identified data are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank all the patients and volunteers for participating in this study. Also, the authors are highly grateful to the anonymous reviewers for their significant and constructive comments and suggestions, which greatly improve the article.

Funding

This work was supported by the National Natural Science Foundation of China (Nos. 82001792) and the Science Foundation of Guangdong Second Provincial General Hospital (No. 3D-A2021009).

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Author notes

  1. Xiaofen Ma

    Present address: The Second School of Clinical Medicine, Southern Medial University, Guangzhou City, Guangdong province, PR China

  2. Yujie Yang and Shishun Fu contributed equally to this work.

Authors and Affiliations

  1. The Second School of Clinical Medicine, Southern Medial University, Guangzhou City, Guangdong province, PR China

    Yujie Yang

  2. Department of Nuclear Medicine, Guangdong Second Provincial General Hospital, No. 466 Road Xingang, Guangzhou, 510317, P. R. China

    Yujie Yang, Shishun Fu, Guihua Jiang, Junzhang Tian & Xiaofen Ma

  3. Department of Neurology, Guangdong Second Provincial General Hospital, No.466 Road Xingang, Guangzhou, 510317, P. R. China

    Guang Xu

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Contributions

Xiaofen Ma and Junzhang Tian: Conceived and designed the experiments, Performed the experiments, Contributed reagents/materials/analysis tools. Yujie Yang and Shishun Fu: Analyzed the data, Figures, Writing-original draft; Guihua Jiang: contributed reagents/materials/analysis tools. Yujie Yang Liu and Guang Xu: Performed the experiments.

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Correspondence to Junzhang Tian or Xiaofen Ma.

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The ethics committee of Guangdong Second Provincial General Hospital in China approved this study and written informed consent was obtained from all participants.

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Yang, Y., Fu, S., Jiang, G. et al. Functional connectivity changes of the hippocampal subregions in anti-N-methyl-D-aspartate receptor encephalitis. Brain Imaging and Behavior (2024). https://doi.org/10.1007/s11682-024-00852-3

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